Efficacy and tolerability of tasipimidine after 3 repeated bed-time doses in patients with insomnia disorder with a 4-week extension part
- Trial ID
- 2022-502483-21-00
- Protocol
- 3110012
- Sponsor
- Orion Corporation
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of tasipimidine in patients diagnosed with **insomnia disorder**. This is clinically relevant as insomnia disorder significantly impacts patients' quality of life, and effective treatments are essential for improving sleep quality and overall health outcomes.
Secondary objectives include:
- Evaluating the **safety** and tolerability of tasipimidine, which is crucial for determining the risk-benefit profile of the treatment.
- Studying the **pharmacokinetics** (PK) of tasipimidine and its metabolite ORM-18662, providing insights into the drug's absorption, distribution, metabolism, and excretion in patients with insomnia disorder.
- Determining the **pharmacokinetic/pharmacodynamic** (PK/PD) relationship, which helps in understanding the drug's effects relative to its concentration in the body.
- Evaluating the efficacy of tasipimidine in patients with insomnia disorder, further supporting the primary objective by assessing the treatment's impact on sleep parameters.
Participants
The clinical trial focuses on evaluating the efficacy of tasipimidine in patients diagnosed with **insomnia disorder**. The study population comprises both male and female subjects aged between 18 and 65 years, inclusive. Participants are required to have a self-reported history of insomnia symptoms, such as taking 30 minutes or more to fall asleep and having a subjective total sleep time of 6 hours or less, occurring on at least three nights per week for a minimum of three months prior to the screening. The trial includes individuals with an Insomnia Severity Index score of 15 or higher in Part 1 and 11 or higher in Part 2. Participants must have a usual bedtime between 21:00 and 02:00 and a regular time in bed ranging from 6 to 9 hours. The trial population was selected based on these criteria, and it includes both genders, with a focus on ensuring that participants adhere to effective contraception methods if applicable. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and tolerability of **tasipimidine** in patients diagnosed with **insomnia disorder**. This study is structured as a randomized, double-blind, placebo-controlled trial, with a primary focus on assessing the impact of tasipimidine on sleep parameters. The trial is divided into two parts, with Part 1 involving a 3-day treatment period and Part 2 extending over 31 days. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on May 1, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, insomnia severity, and sleep patterns. The primary inclusion criteria require participants to have a self-reported history of insomnia symptoms for at least three months, with specific sleep parameters confirmed via polysomnography (PSG). Following the screening, eligible participants will be randomized to receive either the active treatment, ODM-105 oral solution, or a placebo.
Throughout the trial, participants will attend follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments of primary endpoints such as wake after sleep onset (WASO) and latency to persistent sleep (LPS), both measured using PSG. Secondary endpoints will evaluate adverse events, cardiovascular parameters, and pharmacokinetic variables. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted to gather comprehensive data on the trial's outcomes.
Participant involvement is expected to last up to 31 days, depending on the part of the trial they are enrolled in. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial is conducted in accordance with ethical guidelines, ensuring that all participants provide informed consent prior to participation.
Treatment
The clinical trial involves the administration of **tasipimidine** in two different formulations as experimental treatments. The first formulation is ODM-105 0.3 mg/ml oral solution, which is provided by Orion Corporation. This formulation is administered orally, with a maximum daily dose of 680 micrograms and a total maximum dose of 2040 micrograms over a treatment period of 3 days. The active substance, tasipimidine, is of chemical origin. The pharmaceutical form is an oral solution, ensuring ease of administration and compliance monitoring through direct observation and participant self-reporting.
The second experimental formulation is ODM-105 0.05 mg/ml oral solution, also provided by Orion Corporation. This formulation is similarly administered orally, with the same maximum daily dose of 680 micrograms. However, the total maximum dose for this formulation is 21080 micrograms, with a treatment period extending up to 31 days. The active substance remains tasipimidine, and the formulation is designed to maintain consistency in administration and monitoring, similar to the 0.3 mg/ml solution.
In addition to the experimental treatments, a placebo oral solution, labeled as ODM-105 placebo oral solution, is utilized in the study. This placebo is designed to match the experimental formulations in appearance and administration route, ensuring blinding of the study. The placebo does not contain any active substance and serves as a control to evaluate the efficacy and tolerability of tasipimidine in patients with insomnia disorder. Compliance with the placebo administration is monitored in the same manner as the active treatments, ensuring consistency across all study arms.
Efficacy
The efficacy of **tasipimidine** in patients with insomnia disorder will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of Wake After Sleep Onset (WASO) and Latency to Persistent Sleep (LPS), both of which will be assessed using polysomnography (PSG) data collected on Day 1 and Day 2, combined from Part 1 and Part 2 of the trial. Secondary endpoints will encompass a range of parameters, including adverse events (AEs), heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), orthostatic changes in blood pressure, morning sleepiness, safety laboratory tests, and pharmacokinetic (PK) variables. Additionally, WASO and LPS will be assessed separately for Day 1 and Day 2 in both parts of the trial, with further assessments on Day 27 and Day 28 in Part 2.
The efficacy assessments will be conducted using validated tools and methods, such as polysomnography, to ensure accurate and reliable data collection. The schedule for these assessments is structured to capture both immediate and longer-term effects of the treatment, with specific timepoints designated for data collection. This comprehensive approach aims to provide a robust evaluation of the treatment's impact on insomnia disorder, facilitating a thorough analysis of its efficacy and safety profile.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent (IC) for participation in the study.
- Male or female subjects with age between 18 and 65 years (inclusive) at screening visit.
- Insomnia disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Text Revision (DSM-5-TR®).
- Self-reported history of the following on at least 3 nights per week and for at least 3 months prior to the screening: ≥ 30 minutes to fall asleep, subjective total sleep time (sTST) ≤ 6 hours at screening visit.
- Insomnia Severity Index© (ISI©) score ≥ 15 in Part 1 and ≥ 11 in Part 2.
- Usual bedtime between 21:00 and 02:00.
- Regular time in bed between 6 and 9 hours.
- Meeting the following sleep parameter criteria in PSG on the 2 screening PSG nights: mean latency to persistent sleep (LPS) ≥ 25 minutes (with none of the 2 nights < 15 minutes) and mean total sleep time (TST) ≤ 6 h in Part 1 and ≤ 6.5 h in Part 2.
- Female subjects with fertile male partner, and male subjects with female partners of child-bearing potential, must adhere to a highly effective form of contraception, if sexually active and not permanently sterilised. Additionally, women who are postmenopausal (1 year since last menstrual cycle) are considered not to be reproductive and can be included.
Exclusion Criteria
- A predictable poor compliance or inability to understand and comply with protocol requirements, instructions and protocol-stated restrictions, or communicate well with the investigator.
- Body mass index below 18.5 or above 40.0 kg/m2.
- Self-reported usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week.
- Shift work within 2 weeks prior to the screening visit, or planned shift work during the study.
- Travel across ≥ 3 time zones within 2 weeks prior to the screening visit, or planned travel across ≥ 3 time zones during the study.
- Use of medications with known relevant alpha-2 AR affinity (e.g. mirtazapine, mianserine, dexmedetomidine, clonidine, guanfacine or tizanidine) or known strong or moderate CYP2D6 inhibitors (e.g. in Part 1 paroxetine, fluoxetine, bupropion, in both parts quinidine) within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG. As an exception, antidepressants listed in section 5.6.2 are allowed in Part 2.
- Use of benzodiazepines, z-drugs (zolpidem, zopiclone, eszopiclone, zaleplon), melatonin, sedative H1 antagonists, sedative antidepressants (e.g. doxepine and trazodone), orexin receptor antagonists (e.g. daridorexant) or antipsychotics within 7 days or 5 times the half-life, whichever is longer, prior to 1st screening PSGs.
- Use of amphetamine derivatives like methylphenidate, dexamphetamine and lisamphetamine within 14 days, or 5 times the half-life, whichever is longer, prior to the 1st screening PSG.
- Use of other CNS-active drugs, including over-the-counter or herbal medicines, for 7 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG. In Part 2 the use of one of the following antidepressants is allowed: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, bupropion, duloxetine, milnacipran, venlafaxine, vortioxetine, providing that the dose has been stable at least 4 weeks prior to the 1st screening PSG and planned to be stable throughout the study.
- Start of other new chronic medication within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG and in Part 2 also a planned change to an ongoing chronic medication during the study.
- Cognitive behavioural therapy (CBT) for any indication is allowed only if the CBT started at least 1 month prior to the 1st screening PSG and the subject agreed to continue the CBT throughout the study.
- Any lifetime history of a diagnosed sleep-related breathing disorder, including chronic obstructive pulmonary disease and sleep apnoea.
- Acute or unstable psychiatric conditions as judged by the investigator (including but not restricted to current bipolar disorder, schizophrenia or obsessive compulsive disorder) that are diagnosed by the Mini International Neuropsychiatric Interview© (MINI©) or that require pharmacological treatment for these disorders. N.B.: subjects with a history of major depressive disorder or anxiety disorder that are currently stable, and without requiring pharmacological treatment are eligible. In Part 2 antidepressants specified in exclusion criterion 9 and section 5.6.2 are allowed.
- Part 1: positive answer to item 4 or 5 on the Colombia-Suicide Severity Rating Scale (C-SSRS) or current risk of suicide based on the investigator’s judgement at screening visit. Part 2: positive answer to item 4 or 5 in the past 6 months or any suicidal behaviour in the past 10 years or current risk of suicide based on the investigator’s judgement at screening visit.
- Diagnosis of alcohol or substance use disorder within 2 years prior to the screening visit or inability to refrain from drinking alcohol for at least 3 consecutive days.
- Myocardial infarction or other clinically significant ischemic cardiac disease, heart failure, sick-sinus syndrome or arrhythmia tendency within the past 2 years.
- History of clinically significant orthostatic hypotension, syncope or syncopial attacks within the past 2 years.
- Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological (e.g. epilepsy or dementia) or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study.
- Heavy tobacco use (at least one pack of cigarettes a day or corresponding heavy use of other nicotine containing products or inability to refrain from smoking during the night).
- Caffeine consumption ≥ 600 mg per day or regular caffeine consumption after 4 p.m.
- Supine HR < 50 bpm or > 100 bpm after a 5-minute rest at screening visit.
- Systolic blood pressure (SBP) < 100 or > 160 mmHg or diastolic blood pressure (DBP) < 50 or > 100 mmHg after a 5-minute rest at screening visit.
- Orthostatic hypotension (decrease of ≥ 20 mmHg for SBP or decrease of ≥ 10 mmHg for DBP) or dizziness in orthostatic test at screening visit.
- Abnormal 12-lead ECG finding of clinical relevance at the screening visit, (after 5 min rest in supine position, confirmed by a repeat measurement) for example:• QTc (calculated through the Fridericia’s formula) repeatedly > 450 ms in males or > 470 ms in females at screening visit. Pacemaker rhythm as such does not need to lead to exclusion. (If QTc interval measured by the ECG machine algorithm is > 450 ms, 2 additional recordings will be done and QTcF values confirmed) • 2° or 3° AV block.
- AST and/or ALT > 2 × ULN and/or direct bilirubin > 1.5 × ULN.
- Positive urine drug screen or presence of alcohol in exhaled breath at screening visit, screening PSG nights or on Day 1.
- Any other abnormal value in laboratory tests, vital signs or 12-lead ECG which may in the opinion of the investigator interfere with the interpretation of the study results or cause a health risk for the subject if he/she takes part in the study.
- Pre-planned elective surgery for the study period.
- Known hypersensitivity to the active substance or to any of the excipients of the study treatment.
- Pregnant or lactating females.
- Blood donation or loss of significant amount of blood within 60 days prior to the screening.
- Participation in a drug study within 60 days prior to the screening or earlier participation in clinical study with tasipimidine.
- Periodic limb movement disorder with arousal index (PLMAI) ≥ 15/h (assessed on the 1st screening PSG night), restless legs syndrome, circadian rhythm disorder, REM behaviour disorder, or narcolepsy.
- Apnoea/hypopnea index (AHI) ≥ 15/h according to American Academy of Sleep Medicine criteria or event associated with blood oxygen saturation level by pulse oximetry (SpO2) < 80%, as assessed on the 1st screening PSG night.
- Any other condition that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Finland | Not Recruiting | 01 May 2023 | 78 |
 Germany | Not Recruiting | 01 May 2023 | 99 |
 Poland | Not Recruiting | 01 May 2023 | 95 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ODM-105 0.3 mg/ml oral solution | Test | ORAL SOLUTION | ORAL | 680 | 3 | PRD10111295 |
ODM-105 0.05 mg/ml oral solution | Test | ORAL SOLUTION | ORAL | 680 | 31 | PRD11453436 |
ODM-105 placebo oral solution | Placebo | N/A | — | — | — | N/A |